Due to the increasing prevalence of obesity in the global population, body weight management has become a key element of modern healthcare, and more effective means of weight reduction are needed.
Obesity can result from a level of energy intake which exceeds the body's energy expenditure. Reduction of body weight may be achieved via reducing total caloric intake from the diet, or by reducing caloric intake contributed by specific dietary components. For example, caloric intake can be reduced by control of dietary fat consumption or via control of fat absorption in vivo. Because of its role in the pathogenesis of cardiovascular disease, control of fat intake is important.
Lifestyle changes can be difficult to implement, and as physical activity in the developed world continues to decline and Western-style diets are adopted by developing countries, the prevalence of obesity and its associated health problem is expected to increase worldwide. However, the effectiveness of currently available drugs and supplements for promoting weight control or weight loss is very variable, particularly if they are not used in conjunction with a calorie-restricted diet and exercise regimen.
Orlistat has been approved as an anti-obesity drug by the US Food and Drug Administration. Marketed under the names Xenical and Alli, Orlistat inhibits pancreatic lipase activity in the small intestine. Pancreatic lipase breaks down triglycerides into fatty acids and monoglycerides, which are subsequently absorbed into the body. Thus, inhibition of lipase activity effectively reduces fat absorption. A reduced fat diet is recommended while taking this medication. In the absence of a major dietary change, the adverse effects of gastrointestinal discomfort, diarrhea and flatulence have limited its use (See Heck et al, Orlistat, a new lipase inhibitor for the management of obesity, Pharmacotherapy, 20, p 270-279, 2000). There have also been reports of severe liver damage, including cases of liver failure, in patients taking this agent between 1999 and 2008 (US Food and Drug Administration press release 24 Aug. 2009). Another drug, Sibutramine, is a serotonin and norepinephrine reuptake inhibitor, and reduces body weight by suppressing appetite. However, a review by the European Medicines Agency found that the cardiovascular risks of Sibutramine outweigh its benefits. Emerging evidence suggests that there is an increased risk of non-fatal heart attacks and strokes with this medicine.
Because of the side effects of existing drugs such as those discussed above, there is an on-going need to develop new compositions to control body weight and/or treating obesity, and related disorders, such as metabolic syndrome.